Blog Archive

Monday, 7 July 2008

Weekly BioNews 30 June - 7 Jul 2008

- Synthetic molecules emulate enzyme behavior for the first time

July 2, 2008 04:59 PM

When chemists want to produce a lot of a substance -- such as a newly designed drug -- they often turn to catalysts, molecules that speed chemical reactions. Many jobs require highly specialized catalysts, and finding one in just the right shape to connect with certain molecules can be difficult. Natural catalysts, such as enzymes in the human body that help us digest food, get around this problem by shape-shifting to suit the task at hand.

Chemists have made little progress in getting synthetic molecules to mimic this shape shifting behavior -- until now.

Ohio State University chemists have created a synthetic catalyst that can fold its molecular structure into a specific shape for a specific job, similar to natural catalysts.

In laboratory tests, researchers were able to cause a synthetic catalyst -- an enzyme-like molecule that enables hydrogenation, a reaction used to transform fats in the food industry -- to fold itself into a specific shape, or into its mirror image.

The study appears in the June 25 issue of the Journal of the American Chemical Society.

Being able to quickly produce a catalyst of a particular shape would be a boon for the pharmaceutical and chemical industries, said Jonathan Parquette, professor of chemistry at Ohio State.

The nature of the fold in a molecule determines its shape and function, he explained. Natural catalysts reconfigure themselves over and over again in response to different chemical cues -- as enzymes do in the body, for example.

When scientists need a catalyst of a particular shape or function, they synthesize it through a process that involves a lot of trial and error.

"It's not uncommon to have to synthesize dozens of different catalysts before you get the shape you're looking for," Parquette said. "Probably the most important contribution this research makes is that it might give scientists a quick and easy way to get the catalyst that they want."The catalyst in this study is just a prototype for all the other molecules that the chemists hope to make, said co-author and professor of chemistry T.V. RajanBabu....

Researchers at North Carolina State University have found that quantum dot nanoparticles can penetrate the skin if there is an abrasion, providing insight into potential workplace concerns for healthcare workers or individuals involved in the manufacturing of quantum dots or doing research on potential biomedical applications of the tiny nanoparticles.

While the study shows that quantum dots of different sizes, shapes and surface coatings do not penetrate rat skin unless there is an abrasion, it shows that even minor cuts or scratches could potentially allow these nanoparticles to penetrate deep into the viable dermal layer - or living part of the skin - and potentially reach the bloodstream.

Dr. Nancy Monteiro-Riviere, professor of investigative dermatology and toxicology at NC State's College of Veterinary Medicine, tested the ability of the quantum dots to penetrate rat skin at 8 and 24 hour intervals. The experiment evaluated rat skin in various stages of distress - including healthy skin, skin that had been stripped using adhesive tape and skin that had been abraded by a rough surface. The researchers also assessed whether flexing the skin affected the quantum dots' ability to penetrate into the dermal layer. Monteiro-Riviere co-authored the study with doctoral student Leshuai Zhang.

While the study indicates that acute - or short-term - dermal exposure to quantum dots does not pose a risk of penetration (unless there is an abrasion), Monteiro-Riviere notes "there is still uncertainty on long-term exposure." Monteiro-Riviere explains that the nanoparticles may be able to penetrate skin if there is prolonged, repeated exposure, but so far no studies have been conducted to date to examine that possibility. Quantum dots are fluorescent nanoparticles that may be used to improve biomedical imaging, drug delivery and diagnostic testing.

Titanium implants were successfully introduced by P.-I. Brånemark and co-workers in 1969 for the rehabilitation of edentulous jaws. After 40 years of research and development, titanium is currently the most frequently used biomaterial in oral implantology, and titanium-based materials are often used to replace lost tissue in several parts of the body.

There are some alternatives to modulating the body's response after implant placement. Modifying the implant surface topography has been a successful path among the scientific community, with the primary goals of achieving faster bone contact to the implant surface and more predictable results after several years. Today, during the 86th General Session of the International Association for Dental Research, convening here, a team of Swedish researchers is reporting the results of experiments that focused on structures, so-called 'nanostructures', one million times smaller than a Canadian one-dollar coin. The results demonstrated enhanced bone response to dental implants modified with such small structures as soon as 4 weeks after implant placement...

Natural products are highly valued by consumers yet their properties have been difficult to reproduce fully in synthetic materials, placing a drain on our limited natural resources. Until now ...Scientists at the National Physical Laboratory (NPL) are working towards producing the world's first model that will predict how we perceive naturalness. The results could help make synthetic products so good that they are interpreted by our senses as being fully equivalent to the 'real thing', but with the benefits of reduced environmental impact and increased durability.

NPL began undertaking a real-time experiment at the Royal Society's Summer Science Exhibition. The public were invited to touch and feel 20 wood and wood effect samples and vote on whether they are real or not. The exhibition will now be toured around the UK during the next year to collect a census of data from across the country. This will then be used to help build the first predictive model of how we judge naturalness.

As well as the real-time experiment the travelling exhibition will include a range of interactive exhibits that explore the perceptual process. The first of these will show how we can use body parts to measure an object, as the ancient Egyptians did with the cubit, a standard measure related to the Pharaoh's arm length. There are visual, tactile and auditory experiments designed to demonstrate the limitations of the senses as measurement devices, by exposing how perceptions can be fooled by illusions. Videos will highlight the how the use of Magnetic Resonance Imaging (MRI) brain scans is helping us understand the perceptual process, by allowing researchers to discover which areas of the brain are stimulated when people carry out specific tasks, such as using their vision and touch senses to explore natural and non natural wood samples.

The exhibit is part of a much larger EU-funded project undertaken by a unique set of multidisciplinary of researchers called the Measurement of Naturalness (MONAT). This is one of a series of EU projects trying to 'Measure the Impossible', other projects are investigating subjects as diverse as eyewitness memory, emotional response to computer games, measuring body language and understanding how music induced emotions are processed in the brain.

The MONAT team will work over three years to examine how the perceived naturalness of materials is influenced by their physical properties. It includes:

* Neuroscientists who scan the brain activity of individuals as they examine different materials

* Psychologists who measure the way people perceive different materials when they use their hands or eyes, or both

* NPL's experts in metrology, data analysis and software modelling, who contribute expertise in making accurate physical measurements of the properties of different materials and will build the model of perceived naturalness.

The physical characteristics of a surface, such as its colour, texture and surface roughness, are being linked to what is happening in a person's brain when they see or touch the surface. Once this is understood it should be possible to accurately predict what we will perceive as natural, and manufacturers will be able to design synthetic products to meet this expectation. The results could have a great impact on materials such as wood, animal skin and furs, marble and stone, plants and even prosthetics.

- Researchers Are First To Simulate The Binding Of Molecules To A Protein

ScienceDaily (July 3, 2008)

You may not know what it is, but you burn more than your body weight of it every day. Adenosine triphosphate (ATP), a tiny molecule that packs a powerful punch, is the primary energy source for most of your cellular functions.

Now researchers at the University of Illinois have identified a key step in the cellular recycling of ATP that allows your body to produce enough of it to survive. Without this cycling of ATP and its low-energy counterpart, adenosine diphosphate (ADP), into and out of the mitochondrion, where ADP is converted into ATP, life as we know it would end.

Researchers have for the first time simulated the binding of ADP to a carrier protein lodged in the inner membrane of the mitochondrion. It is the first simulation of the binding of a molecule to a protein.

As its name indicates, ATP contains three phosphate groups. The energy produced when one of these groups is detached from the molecule drives many chemical reactions in the cell. This process also yields ADP, which must go through the ADP/ATP carrier (AAC) to get into the mitochondrion to be converted back into ATP.

The AAC acts a lot like a revolving door: For each molecule of ADP going into the mitochondrion, one ATP gets booted out. These two activities are not simultaneous, however. The carrier is either shuttling ADP into the mitochondrion or ejecting ATP into the wider environment of the cell, where it can be put to use...

View of the ATP/ADP carrier from the cytoplasm, with the ADP molecule (blue, aqua, red and white spheres) at the entrance, ready to be funneled into the carrier. (Credit: Image courtesy of Emad Tajkhorshid and Yi Wang, U. of I.)

A puzzle in the control of cell division, one of the most fundamental processes in all biology, has been unravelled by Oxford University researchers. Although the steps of cell division are familiar to all pupils studying biology in schools, the details of how cell division is controlled and errors avoided have still to be sorted out.

In a new paper in Nature, the Oxford team show that a protein ring is used to hold two sister copies of each DNA molecule together physically until they are ready to be segregated into each daughter cell after division.

Understanding the mechanics of cell division is important: mis-separation of chromosomes can be one of the defining characteristics of cancerous cells, and such errors are also a leading cause of infertility in women as they get older. Down’s syndrome – the presence of an extra copy of chromosome 21 – is one example of what can happen when chromosome segregation goes wrong.

‘DNA replication and cell division provides the mechanism for evolution,’ explains Professor Kim Nasmyth, head of the Department of Biochemistry at the University of Oxford. ‘It is the most fundamental process in biology, and chromosome segregation is one of the driving forces.’

Cell division, or mitosis, produces new cells through the growth and division of existing cells. The process begins with the replication of the genetic material held in the chromosomes of the cell. The pairs of sister DNA molecules or chromatids are lined up before being pulled in opposite directions to different sides of the cell. Partitioning of the original cell then gives two new daughter cells each with the full complement of chromosomes....

As the specter of a worldwide outbreak of avian or “bird flu” lingers, health officials recognize that new drugs are desperately needed since some strains of the virus already have developed resistance to the current roster of anti-flu remedies.

Now, a team of UC San Diego scientists - with the help of resources at the San Diego Supercomputer Center (SDSC), also at UC San Diego - have isolated more than two dozen promising and novel compounds from which new “designer drugs” might be developed to combat this disease. In some cases, the compounds appeared to be equal or stronger inhibitors than currently available anti-flu remedies.

“If those resistant strains begin to propagate, then that’s when we’re going to be in trouble, because we don’t have any anti-virals active against them,” said Rommie Amaro, a postdoctoral fellow in chemistry at UC San Diego. “So, we should have something as a backup, and that’s exactly why we’re working on this.”

Avian flu has provoked considerable concern since humans have little or no immune protection against the virus. While flu vaccines are being developed, it could take up to nine months for an effective vaccine to be developed against any new strains, and could still be rendered ineffective if any new strains arise over that time. Should the virus gain the capacity to spread from person to person, the result could be a worldwide outbreak or pandemic...

Using protein structures generated by supercomputers, these renderings of the neuraminidase enzyme may help scientists identify potential new drug candidates to fight Avian flu, as strains of the disease become ever more resistant. Potential candidate drugs are shown docked into the neuraminidase active site in panels A-D. Panel A shows the crystal structure protein; panels B-D show proteins generated with molecular dynamics simulations. The images were generated with the Adaptive Poisson Boltzmann Solver (APBS) and Python Molecular Viewer (PMV). (Credit: Rommie E. Amaro, Lily S. Cheng, UC San Diego. Source: San Diego Supercomputer Center, UC San Diego.)